Latinos, the largest ethnic minority group in the United States, have a high prevalence of hypertension, diabetes and obesity and also experience higher rates of poverty and social stressors in both childhood and adulthood compared to other racial/ethnic groups. There is extensive evidence that economic and social stressors shape the development of cardiometabolic health. However, it is largely unknown how these stressors affect biological processes, particularly at the cellular level. One novel method to evaluate possible mechanisms underlying the associations between social stressors and cardiometabolic health across the life course is DNA methylation (DNAm). Recently a handful of small cross-sectional studies have found that stressful experiences may alter DNAm, thus providing a potential mechanism by which social stress may get under the skin. Most of the existing health research among Latinos has been specific to Latinos of Mexican origin. Latinos are not a homogenous group and while some Latinos are at greater risk of certain chronic conditions, other Latino groups may be at lower risk for certain conditions. Examining what factors may confer risk to some Latino ethnic groups or protect other Latino ethnic groups is crucial for developing interventions and informing decisions about resource allocation. We propose to examine the association between social and economic stressors, across the life course in relation to DNAm, as well as the rate of change of methylation and changes in cardiometabolic health, using existing data from the Hispanic Community Health Study /Study of Latinos (HCHS/SOL). The HCHS/SOL study is a longitudinal study of US Latinos, representing varied countries of origin, conducted in the US. We propose to use existing data from a stratified random sample of 500 men and 500 women, who completed an extensive set of socio-economic and stress measures in the HCHS/SOL Sociocultural Ancillary study and who provided blood samples at two different time points six years apart in adulthood. Existing blood samples will be assayed for genome-wide DNAm and DNAm age. Cardiometabolic health markers (obesity, diabetes, hypertension and lipids) have also been assessed at two time points. Existing data also includes repeated assessments of social and economic stressors and socio-cultural factors (i.e., nativity, familism, acculturation, social support). Specifically, we will examine 1) whether social and economic stressors in childhood and adulthood are associated with changes in DNAm age and genome-wide methylation over a 6-year period; 2) whether sociocultural factors modify the association between stressors and changes in DNAm and 3) whether DNAm is associated with changes in cardiometabolic health over a 6-year period. Upon completion of this project, our findings will advance understanding of how social and economic stressors shape epigenetic pathways, what factors may exacerbate or ameliorate these pathways and whether epigenetic changes over time influence cardiometabolic health changes.